Junya Ozawa

Contribution of knee adduction moment impulse to pain and disability in Japanese women with medial knee osteoarthritis.

BACKGROUND An increase in the knee adduction moment is one of the risk factors of medial knee osteoarthritis. This study examined the relationship between knee adduction moment and self-reported pain and disability. We also investigated the influence of pain on the relationships between knee adduction moment and gait performance and disability. METHODS Thirty-eight Japanese women with medial knee osteoarthritis participated in this study (66.37 years (41-79 years)). Gait analysis involved the measurement of the external knee adduction moment impulse in the stance duration and during 3 subdivisions of stance. The total, pain and stiffness, and physical function Japanese Knee Osteoarthritis Measure scores were determined. FINDINGS The pain and stiffness, physical function, and total scores were positively correlated with the knee adduction moment impulses in the stance duration, and initial and second double support interval, and single limb support interval. The knee adduction moment impulse during the stance duration was related to the pain and stiffness subscale and gait velocity. The pain and stiffness subscale was related to the physical function subscale. INTERPRETATION Our results suggest that increasing in the knee adduction moment impulse, a proxy for loading on the medial compartment of the knee, is related to increased pain during weight-bearing activities such as walking, thereby restricting walking performance and causing disability by reducing gait velocity. Thus, the reduction in the knee adduction moment impulse during gait may result in pain relief and may serve as a conservative treatment option with disease-modifying potential.

Efficacy of strengthening or aerobic exercise on pain relief in people with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

Objective: We performed a systematic review and meta-analysis of randomized controlled trials to investigate the differences in the efficacies between strengthening and aerobic exercises for pain relief in people with knee osteoarthritis. Data sources: This search was applied to Medline, Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature. All literature published from each source’s earliest date to March 2013 was included. Review methods: Trials comparing the effects of exercise intervention with those of either non-intervention or psycho-educational intervention were collected. Meta-analysis was performed for trials in which therapeutic exercise was carried out with more than three sessions per week up to eight weeks, for pain in people with knee osteoarthritis. All trials were categorised into three subgroups (non-weight-bearing strengthening exercise, weight-bearing strengthening exercise, and aerobic exercise). Subgroup analyses were also performed. Results: Data from eight studies were integrated. Overall effect of exercise was significant with a large effect size (standardised mean difference (SMD): −0.94; 95% confidence interval −1.31 to −0.57). Subgroup analyses showed a larger SMD for non-weight-bearing strengthening exercise (−1.42 [−2.09 to −0.75]) compared with weight-bearing strengthening exercise (−0.70 [−1.05 to −0.35]), and aerobic exercise (−0.45 [−0.77 to −0.13]). Conclusion: Muscle strengthening exercises with or without weight-bearing and aerobic exercises are effective for pain relief in people with knee osteoarthritis. In particular, for pain relief by short-term exercise intervention, the most effective exercise among the three types is non-weight–bearing strengthening exercise.

Effects of aging and exercise training on the histological and mechanical properties of articular structures in knee joints of male rat

The impact of aging on joints can have a profound effect on an individual’s functioning. Our objectives were to assess the histological and mechanical properties of the knee joint capsule and articular cartilage with aging, and to examine the effects of exercise on age-related changes in the knee joint. 2-year-old Wistar rats were divided into a sedentary control group and an exercise-trained group. 10-week-old animals were used to investigate the changes with aging. The joint capsule and cartilage were evaluated with histological, histomorphometric, immunohistochemical, and mechanical analyses. Severe degenerative changes in articular cartilage were observed with aging, whereas exercise apparently did not have a significant effect. The articular cartilage of aged rats was characterized by damage to the cartilage surface, cell clustering, and an abnormal cartilage matrix. Histomorphometric analysis further revealed changes in cartilage thickness as well as a decreased number of chondrocytes. Aging led to stiffness of the articular cartilage and reduced the ability to dissipate the load and distribute the strain generated within the joint. Joint stiffness with aging was independent of capsular stiffness and synovitis was not a characteristic feature of the aging joint. This study confirms that aging alone eventually leads to joint degeneration in a rat model. The lack of recovery in aging joint changes may be due to several factors, such as the duration of the intervention and the regeneration ability of the cartilage.

Effects of exercise therapy on walking ability in individuals with knee osteoarthritis: a systematic review and meta-analysis of randomised controlled trials

Objective: To examine the effect of exercise therapy on the walking ability of individuals with knee osteoarthritis. Data sources: Randomised clinical trials (RCTs) were identified by searching through PubMed, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, and Cumulative Index to Nursing and Allied Health Literature. All literature published to October 2014 were included in the search. Review methods: Data were collected from RCTs that compared the effects of exercise therapy on walking ability with the effects of no intervention or psychoeducational intervention in participants with knee osteoarthritis. The outcome data on the total distance walked (6-minute walk test); the amount of time spent walking (the time to walk arbitrary distances); and gait velocity were obtained and analysed. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. Results: Twenty-eight RCTs were identified. Meta-analysis provided very-low-quality evidence that exercise therapy increased the total distance walked in the 6-minute walk test, in comparison with the effects of the control interventions (SMD = 0.44, 95% CI 0.27 to 0.60). Meta-analysis also provided low- or moderate-quality evidence that the amount of time spent walking and gait velocity were improved more by exercise therapy than by the control interventions (the amount of time spent walking: SMD = −0.50, 95% CI −0.70 to −0.30; gait velocity: SMD = 1.78, 95% CI 0.98 to 2.58). Conclusion: In individuals with knee osteoarthritis, exercise therapy can improve the amount of time spent walking, gait velocity, and maybe the total distance walked.

Effect of the Frequency and Duration of Land-based Therapeutic Exercise on Pain Relief for People with Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

[Purpose] This study aimed to investigate the influence of land-based exercise frequency and duration on pain relief for people with knee osteoarthritis (OA). [Subjects and Methods] The systematic review included randomized controlled trials that investigated this influence, which were identified by searches of PubMed, the Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature. The exercise groups in the identified trials were categorized according to their type, frequency, and duration of exercise, and subgroup analyses were performed. [Results] Data integration of 17 studies (23 exercise groups) revealed a significant effect and a medium effect size. In subgroups involving strengthening exercise programs of ≥9 weeks duration, heterogeneity was found between subjects who performed up to 3 sessions/week and those who performed ≥4 sessions/week. In subgroups involving strengthening exercise programs of up to 3 sessions/week, there was heterogeneity between subjects who exercised for up to 8 weeks and those who exercised for ≥9 weeks. Heterogeneity was not confirmed in aerobic exercise subgroups. [Conclusion] Differences in exercise frequency and duration influence pain relief in effects of strengthening exercises but do not influence the effect size of aerobic exercise for people with knee OA.

Morphological changes in hind limb muscles elicited by adjuvant-induced arthritis of the rat knee

We investigated qualitative and quantitative changes in rat hind limb muscles caused by complete Freunds adjuvant (CFA)‐induced knee joint pain. One week after CFA injection, muscle atrophy was induced only on the CFA‐injected side. Wet weight of the rectus femoris (RF) and soleus (SOL) muscles were significantly decreased by 20% and 19%, respectively. The reduction in cross‐sectional areas by CFA was similar for fast and slow muscle fibers in the RF (10% vs 15%, respectively) and SOL muscles (16% vs 16%, respectively). At the light microscopic level, pathological changes were not found in the RF muscles on both sides, although the infiltration of mononuclear cells and muscle regeneration were found in the SOL muscles on CFA‐injected and contralateral control sides. On the other hand, electron microscopy revealed degenerative changes in the RF and SOL muscles on the CFA‐injected side. Interestingly, sarcomere hypercontraction, indicating overexercise, was observed to a limited extent in the SOL muscles on the control side. In conclusions, knee joint pain can trigger the rapid development of muscle atrophy with degenerative changes not only in thigh but also calf muscles. This indicates that early interventions to inhibit joint pain or inflammation may prevent muscle atrophy.

Does exercise therapy improve the health-related quality of life of people with knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials

[Purpose] The aim of this study was to examine the effects of exercise therapy on the health-related QOL of people with knee osteoarthritis. [Subjects] Four databases (PubMed, Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature) were searched for randomized controlled trials that evaluated the effects of exercise therapy on health-related QOL assessed by the SF-36 for inclusion in our systematic review. The methodological qualities of the trials were assessed independently by two reviewers using the PEDro scale. Pooled analyses with a random-effects model or a fixed-effects model were used in the meta-analyses to calculate the standardized mean differences and 95% confidence intervals. [Results] Twelve studies met the inclusion criteria. Our meta-analysis provides high-quality evidence that exercise therapy increases the summary score, physical functioning score, and role-physical score of knee osteoarthritis sufferers. Our meta-analysis also provides moderate-quality evidence that the physical component summary and mental component summary scores were improved to a greater extent by exercise therapy than by control interventions. [Conclusion] Exercise therapy can improve health-related QOL, as assessed by the SF-36, of knee osteoarthritis sufferers.

Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with Special Reference to Inflammatory Cytokines.

Pressure ulcers have been investigated in a few animal models, but the molecular mechanisms of pressure ulcers are not well understood. We hypothesized that pressure results in up-regulation of inflammatory cytokines and those cytokines contribute to the formation of pressure ulcers. We measured genome-wide changes in transcript levels after compression, and focused especially on inflammatory cytokines. The abdominal wall of rats was compressed at 100 mmHg for 4 hours by two magnets. Specimens were obtained 12 hours, 1, or 3 days after compression, and analyzed by light microscopy, microarray, Real-Time PCR, and ELISA. The skin and subcutaneous tissue in the compressed area were markedly thickened. The microarray showed that numerous genes were up-regulated after the compression. Up-regulated genes were involved in apoptosis, inflammation, oxidative stress, proteolysis, hypoxia, and so on. Real-Time PCR showed the up-regulation of granulocyte-macrophage colony stimulating factor (GM-CSF), interferon γ (IFN-γ), interleukin 1β (IL-1β), interleukin 1 receptor antagonist gene (IL1Ra), interleukin 6 (IL-6), interleukin 10 (IL-10), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 1 (TIMP-1), and tumor necrosis factor α (TNF-α) at 12 hours, IFN-γ, IL-6, IL-10, MMP-3, and TIMP-1 at 1 day, and IFN-γ, IL-6, and MMP-3 at 3 days. Some genes from subcutaneous tissue were up-regulated temporarily, and others were kept at high levels of expression. ELISA data showed that the concentrations of IL-1β and IL-6 proteins were most notably increased following compression. Prolonged up-regulation of IL-1β, and IL-6 might enhance local inflammation, and continuous local inflammation may contribute to the pressure ulcer formation. In addition, GM-CSF, IFN-γ, MMP-3, and TIMP-1 were not reported previously in the wound healing process, and those genes may have a role in development of the pressure ulcers. Expression data from Real-Time PCR were generally in good agreement with those of the microarray. Our microarray data were useful for identifying genes involved in pressure ulcer formation. However, the expression levels of the genes didn’t necessarily correspond with protein production. As such, the functions of these cytokines need to be further investigated.

Development of arthrogenic joint contracture as a result of pathological changes in remobilized rat knees.

This study aimed to elucidate how rats recover from immobilization‐induced knee joint contracture. Rats’ right knees were immobilized by an external fixator at a flexion of 140° for 3 weeks. After removal of the fixator, the joints were allowed to move freely (remobilization) for 0, 1, 3, 7, or 14 days (n = 5 each). To distinguish myogenic and arthrogenic contractures, the passive extension range of motion was measured before and after myotomy of the knee flexors. Knee joints were histologically analyzed and the expression of genes encoding inflammatory or fibrosis‐related mediators, interleukin‐1β (1L‐1β), fibrosis‐related transforming growth factor‐β1 (TGF‐β1), and collagen type I (COL1A1) and III (COL3A1), were examined in the knee joint posterior capsules using real‐time PCR. Both myogenic and arthrogenic contractures were established within 3 weeks of immobilization. During remobilization, the myogenic contracture decreased over time. In contrast, the arthrogenic contracture developed further during the remobilization period. On day 1 of remobilization, inflammatory changes characterized by edema, inflammatory cell infiltration, and upregulation of IL‐1β gene started in the knee joint posterior capsule. In addition, collagen deposition accompanied by fibroblast proliferation, with upregulation of TGF‐β1, COL1A1, and COL3A1 genes, appeared in the joint capsule between days 7 and 14. These results suggest the progression of arthrogenic contracture following remobilization, which is characterized by fibrosis development, is possibly triggered by inflammation in the joint capsule. It is therefore necessary to focus on developing new treatment strategies for immobilization‐induced joint contracture.

Nociception contributes to the formation of myogenic contracture in the early phase of adjuvant‐induced arthritis in a rat knee

It is unknown how joint contracture is generated in inflamed joints. This study aimed to clarify the role of nociception on the formation of joint contracture secondary to arthritis. Monoarthritis was induced by intra‐articular injections of complete Freunds adjuvant (CFA) into rat knees. On day 5 after CFA injection, the passive extension range of motion (ROM) of knee joints were measured, both before and after myotomy of knee flexors, to evaluate the extent of muscular contribution to CFA‐induced joint contracture. The steroidal anti‐inflammatory drug dexamethasone could prevent ROM restrictions completely, both before and after myotomy. On the other hand, the opioid analgesic drug morphine did not prevent the development of restricted ROM observed after myotomy, while it did before myotomy. This indicates that nociception contributes to joint contracture through alterations in muscular structure (myogenic factors). Next, we tested the hypothesis that nociception‐induced reflexive flexor muscle contractions cause myogenic contracture in arthritic joints. To do this, chemical denervation was performed by Botulinum toxin type A (BTX‐A) injections into knee flexor muscles, simultaneously with CFA injections into the knee. As expected, BTX‐A could alleviate ROM restrictions observed before myotomy. These findings suggest that nociceptive‐related muscle contractions play an essential role in the formation of joint contracture. Thus, our study indicates that analgesic management during an early stage of joint arthritis is an essential mean to prevent the formation of joint contracture.